Toxin-antitoxin (TA) systems are small genetic elements which encode toxin proteins that interfere with vital cellular functions. PepA1 and PepG1 toxin proteins, known also as SprA1 and SprG1, are type I TA. In Staphylococcus aureus (S. aureus), their expression without the antitoxin counterparts (SprA1AS and SprF1), is lethal to the pathogen. Molecular Dynamics (MD) simulation was performed for PepA1 and PepG1 to understand their dynamic state, conformational changes, and their toxicity. The protein structures were constructed and used for MD simulation and the conformational changes, stability, flexibility, fluctuations, hydrophobicity, and role of their dynamic state on function prediction were studied extensively by GROMACS MD simulation analysis tools. In silico study indicated that the PepA1 and PepG1 proteins change their structural conformation from an open to closed state where PepA1 conformational changes were faster (10 ns) than PepG1 (20 ns) while PepG1 exerted more stability and flexibility than PepA1. According to SASA values, PepG1 is more hydrophobic than the PepA1 and forms fewer hydrogen bonds than PepA1. The in vivo study with PepA1 and PepG1 proteins provided evidence that both the conformation changes between the open and closed states and the amino acid sequence are crucial for peptide toxicity.

• MeSH
• antitoxiny * metabolismus   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• peptidy metabolismus   MeSH
• stafylokokové infekce * genetika   MeSH
• Staphylococcus aureus metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

This study characterized five Cronobacter spp. and six Salmonella spp. strains that had been isolated from 155 samples of powdered infant formula (PIF) sold in Chile and manufactured in Chile and Mexico in 2018-2020. Two strains of Cronobacter sakazakii sequence type (ST) ST1 and ST31 (serotypes O:1 and O:2) and one strain of Cronobacter malonaticus ST60 (O:1) were identified. All Salmonella strains were identified as Salmonella Typhimurium ST19 (serotype O:4) by average nucleotide identity, ribosomal multilocus sequence typing (rMLST), and core genome MLST (cgMLST). The C. sakazakii and C. malonaticus isolates were resistant to cephalothin, whereas the Salmonella isolates were resistant to oxacillin and ampicillin. Nineteen antibiotic resistance genes were detected in the C. sakazakii and C. malonaticus isolates; the most prevalent were mcr-9.1, blaCSA , and blaCMA . In Salmonella, 30 genes encoding for aminoglycoside and cephalosporin resistance were identified, including aac(6')-Iaa, β-lactamases ampH, ampC1, and marA. In the Cronobacter isolates, 32 virulence-associated genes were detected by WGS and clustered as flagellar proteins, outer membrane proteins, chemotaxis, hemolysins, invasion, plasminogen activator, colonization, transcriptional regulator, survival in macrophages, use of sialic acid, and toxin-antitoxin genes. In the Salmonella strains, 120 virulence associated genes were detected, adherence, magnesium uptake, resistance to antimicrobial peptides, secretion system, stress protein, toxin, resistance to complement killing, and eight pathogenicity islands. The C. sakazakii and C. malonaticus strains harbored I-E and I-F CRISPR-Cas systems and carried Col(pHHAD28) and IncFIB(pCTU1) plasmids, respectively. The Salmonella strains harbored type I-E CRISPR-Cas systems and carried IncFII(S) plasmids. The presence of C. sakazakii and Salmonella in PIF is a health risk for infants aged less than 6 months. For this reason, sanitary practices should be reinforced for its production and retail surveillance.

• Publikační typ
• časopisecké články MeSH

Under stressful conditions, bacterial RelA-SpoT Homolog (RSH) enzymes synthesize the alarmone (p)ppGpp, a nucleotide second messenger. (p)ppGpp rewires bacterial transcription and metabolism to cope with stress, and, at high concentrations, inhibits the process of protein synthesis and bacterial growth to save and redirect resources until conditions improve. Single-domain small alarmone synthetases (SASs) are RSH family members that contain the (p)ppGpp synthesis (SYNTH) domain, but lack the hydrolysis (HD) domain and regulatory C-terminal domains of the long RSHs such as Rel, RelA, and SpoT. We asked whether analysis of the genomic context of SASs can indicate possible functional roles. Indeed, multiple SAS subfamilies are encoded in widespread conserved bicistronic operon architectures that are reminiscent of those typically seen in toxin-antitoxin (TA) operons. We have validated five of these SASs as being toxic (toxSASs), with neutralization by the protein products of six neighboring antitoxin genes. The toxicity of Cellulomonas marina toxSAS FaRel is mediated by the accumulation of alarmones ppGpp and ppApp, and an associated depletion of cellular guanosine triphosphate and adenosine triphosphate pools, and is counteracted by its HD domain-containing antitoxin. Thus, the ToxSAS-antiToxSAS system with its multiple different antitoxins exemplifies how ancient nucleotide-based signaling mechanisms can be repurposed as TA modules during evolution, potentially multiple times independently.

• MeSH
• adeninnukleotidy metabolismus   MeSH
• Bacteria růst a vývoj   metabolismus   MeSH
• bakteriální proteiny metabolismus   MeSH
• databáze genetické MeSH
• fyziologický stres fyziologie   MeSH
• guanosinpentafosfát metabolismus   MeSH
• guanosintetrafosfát metabolismus   MeSH
• guanosintrifosfát metabolismus   MeSH
• ligasy metabolismus   MeSH
• pyrofosfatasy metabolismus   MeSH
• regulace genové exprese u bakterií genetika   MeSH
• signální transdukce MeSH
• systémy toxin-antitoxin fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Vancomycin-resistant enterococci (VRE) are nosocomial pathogens of increasing medical importance. This study involved 121 VRE selectively obtained from a representative set of 1464 samples collected from various sources in the north-eastern part of the Czech Republic. In total, 119 VRE belonged to Enterococcus faecium and two to Enterococcus faecalis. All isolates of E. faecium were resistant to at least three antibiotic classes. The resistance genes vanA, erm(B), tet(M), tet(L), aac(3)-IIIa and aac(6')-aph(2'') were detected. We assigned the E. faecium to sequence types ST5, ST18, ST38, ST64, ST92, ST273, ST549 and ST640. In E. faecium isolates, we identified the presence of replicases rep20pLG1 , rep2pRE25 , rep17pRUM , rep21pVEF1/2 and rep14pRI1 , as well as relaxases relpEF1 , relpLG1 , relpCIZ2 , relpRE25 and relpRUM . The presence of the toxin-antitoxin system axe-txe was detected mainly among isolates of hospital origin. The A and D types of transposon Tn1546 were those occurring most frequently. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first extensive study of vancomycin-resistant enterococci of diverse origin in a single well-defined area of the Czech Republic. The isolates were investigated for their antibiotic resistance, epidemiological characteristics and plasmid characteristics. Based on the results obtained, we can make assumptions as to the ways that vancomycin resistance is disseminated throughout the environment including humans and animals.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální proteiny genetika   MeSH
• Enterococcus faecalis účinky léků   genetika   izolace a purifikace   MeSH
• Enterococcus faecium účinky léků   genetika   izolace a purifikace   MeSH
• enterokoky rezistentní vůči vankomycinu klasifikace   genetika   izolace a purifikace   MeSH
• grampozitivní bakteriální infekce epidemiologie   mikrobiologie   MeSH
• lidé MeSH
• plazmidy genetika   MeSH
• rezistence na vankomycin genetika   MeSH
• systémy toxin-antitoxin genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Kniha je reedicí čtyřsvazkové učebnice lékařské chemie Jana Horbaczewského (1854–1942), která původně vyšla v nakladatelství Grosman a Svoboda mezi lety 1904–1908. Nakladatelská anotace. Kráceno; První česká učebnice lékařské chemie, která vychází opět po 111 letech u příležitosti 165. výročí narození autora.

• Klíčová slova
• chemie fyziologická,
• MeSH
• anorganická chemie MeSH
• organická chemie MeSH
• Publikační typ
• monografie MeSH
• učebnice MeSH

• Konspekt
• Chemie. Mineralogické vědy
• NLK Obory
• chemie, klinická chemie

• MeSH
• antibakteriální látky škodlivé účinky   MeSH
• Bacteria růst a vývoj   účinky léků   MeSH
• bakteriální léková rezistence * účinky léků   MeSH
• biofilmy účinky léků   MeSH
• guanosinpentafosfát MeSH
• lidé MeSH
• quorum sensing účinky léků   MeSH
• SOS odpověď (genetika) účinky léků   MeSH
• systémy toxin-antitoxin účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Toxin-antitoxin systems (TAS) emerged more than 25 years ago and developed as an important field in molecular microbiology. TAS are autoregulated operons coding a stable toxin and an unstable antitoxin found in plasmids and chromosomes of Bacteria and Archaea. The conditional activation of their toxins interferes with cell growth/viability and, depending on the context, can influence plasmid maintenance, stress management, bacterial persistence, cell differentiation and, likely, bacterial virulence. This review summarizes recent results on the parD system of plasmid R1 and on the chromosomal relBE systems found in Escherichia coli and in Streptococcus pneumoniae with a focus on the RNase activity of their toxins, their regulation and their biomedical applications and implications.

• MeSH
• antitoxiny genetika   imunologie   metabolismus   MeSH
• bakteriální toxiny genetika   imunologie   metabolismus   MeSH
• biotechnologie metody   trendy   MeSH
• buňky - růstové procesy genetika   imunologie   MeSH
• financování organizované MeSH
• inhibitory syntézy proteinů imunologie   metabolismus   MeSH
• lidé MeSH
• mikrobiologie trendy   MeSH
• molekulární biologie metody   trendy   MeSH
• plazmidy genetika   MeSH
• ribonukleasy genetika   imunologie   toxicita   MeSH
• ribozomy genetika   imunologie   MeSH
• RNA genetika   imunologie   toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Z původního textu, který v současné době skýtá nejdokonalejší přehled o tématu, byly přeloženy vybrané kapitoly. Úvod seznamuje s terminologií a chemickou podstatou antigenů a protilátek. Poté jsou probírány precipitační a inhibiční reakce, aglutinace a skupina pěti sérových faktorů, tvořících cytotoxický reakční systém, tzv. komplement. První část uzavírá pojednání o anafylaxi, alergii a o vlastnostech protilátek. Druhá část se zabývá metodami stanovení antigenů a křížovými reakcemi. Závěr uvádí speciální metody imunochemického výzkumu a jejich kombinace.

• MeSH
• antigeny MeSH
• imunita MeSH
• imunochemie MeSH
• protilátky MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie
• biochemie

• MeSH
• antitoxiny MeSH
• biologické toxiny MeSH
• Escherichia coli MeSH
• komplement MeSH

• MeSH
• alergologie a imunologie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie